Immunohistochemical BCL-2 and Ki-67 expression predict survival in prostate cancer patients followed expectantly

Borre, Michael; Srausbol-Gron, B; Nostrom, B; Overgaard, Jens

doi:10.1038/sj.pcan.4500252

Cited by 25 publications

(10 citation statements)

References 18 publications

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“…This is reflected further in an association between expression of Ki‐67 and epidermal growth factor receptor,993 mutant p53,994, 995 chromosomal aberrations,996 and perineural invasion 997. Taken together, these findings suggest that Ki‐67 expression may be a weak prognostic indicator of disease recurrence,988, 998–1001 disease progression,70, 991, 992, 1002 and survival 995, 998, 1003, 1004. Biopsy and radical prostatectomy concordance for MIB‐1 in cancer is low 918…”

Section: 0 Goalsmentioning

confidence: 86%

Human prostate cancer risk factors

Bostwick

Burke

Djakiew

et al. 2004

Cancer

499

359

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Section: 0 Goalsmentioning

confidence: 86%

Human prostate cancer risk factors

Bostwick

Burke

Djakiew

et al. 2004

Cancer

499

359

View full text Add to dashboard Cite

“…Today, the immunohistochemical demonstration of Ki-67-MIB-1 positivity in paraffin tissue sections is the most popular approach for measuring the growth fraction of benign and malignant cell populations. Many studies have correlated the findings for MAb Ki67 and MIB-1 with the histological grade, clinical behavior, and outcome of different types of tumors [10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Role and prognostic significance of the Ki‐67 index in non‐Hodgkin's lymphoma

et al. 2009

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Expression of Ki-67, a nuclear antigen protein present in all cycling cells, is used to determine the growth fraction of tumors. The aim of this study was to evaluate the role and prognostic significance of the Ki-67 proliferation index (PI) in non-Hodgkin's lymphoma. Ki-67 was assayed immunohistochemically in tissue samples of 319 patients with newly-diagnosed non-Hodgkin's lymphoma. In 268 patients, the Ki-67 PI was correlated with clinical course and outcome. The mean Ki-67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45% in 85% of aggressive lymphomas (AUC 5 0.877, P < 0.001). In patients with diffuse large B-cell lymphoma (n 5 141), a Ki-67 PI of 70% was found to significantly discriminate patients with good or bad prognosis (AUC 5 0.65, P 5 0.004). Three-year survival was 75% ± 5.6% in patients with a low Ki-67 index compared with 55.9% ± 6% in patients with a high index (P 5 0.015). In patients with a low IPI (≤2), 3-year survival was 94% ± 4% in those with a Ki-67 index ≤70% and 64% ± 8.1% in those with a higher index (P 5 0.002); in patients with bulky disease (>10 cm), the corresponding 3-year survival by Ki-67 index was 100% and 25% ± 12% (P 5 0.012). Our results suggest that the mean Ki-67 PI differs by type of lymphoma. A cut-off value of 45% can help differentiate indolent from aggressive disease. In diffuse large B-cell lymphoma, a cut-off value of 70% can distinguish patients with a good and bad prognosis when combined with other prognostic factors of low IPI score and bulky disease. Am. J. Hematol. 84:338-343, 2009. V

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“…Bcl‐2 is an inner mitochondrial membrane protein that acts to suppress apoptosis by forming inactivating dimers with pro‐apoptotic proteins such as Bax. Bcl‐2 is overexpressed in ˜50% of advanced prostate cancers, and its presence is strongly predictive of poor prognosis, disease progression, the development of hormone resistance and survival ( p = 0.0015) 28. Significantly, both docetaxel29 and other garlic components SAC and DATS have previously been shown to potently inactivate Bcl‐2,22, 30 and SAC has also been observed to significantly decrease its expression in prostate cancer xenograft models 21.…”

Section: Discussionmentioning

confidence: 99%

Evidence of a novel docetaxel sensitizer, garlic‐derived S‐allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer

Howard

Lee

Chiu

et al. 2008

Intl Journal of Cancer

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The recent introduction of docetaxel in the treatment of hormone refractory prostate cancer (HRPC) has made a small but significant impact on patient survival. However, its effect is limited by intolerance and resistance. The aim of our study was to investigate if the garlic-derived compound, S-allylmercaptocysteine (SAMC), was able to act as a docetaxel sensitizing agent. First, the effect of SAMC on docetaxel sensitivity was examined on 3 HRPC cell lines by colony forming assay. We found that SAMC increased the efficacy of docetaxel on colony forming inhibition by 9-50% compared to single agent treatment. Second, using the HRPC CWR22R nude mice model, we found that the combination of SAMC and docetaxel was 53% more potent than docetaxel alone (p 5 0.037). In addition, there was no additive toxicity in the mice treated with the combination therapy evidenced by histological and functional analysis of liver, kidney and bone marrow. These results suggest that SAMC is able to increase the anticancer effect of docetaxel without causing additional toxic effect in vivo. Third, flow cytometry and Western blotting analysis on HRPC cell lines demonstrated that SAMC promoted docetaxel-induced G2/M phase cell cycle arrest and apoptotic induction. In addition, immunohistochemistry on CWR22R xenograft revealed a suppression of Bcl-2 expression and upregulation of E-cadherin in the SAMC and docetaxel treated animals. These results suggest that SAMC may promote docetaxel-induced cell death through promoting G2/ M cell cycle arrest and apoptosis. Our study implies a potential role for SAMC in improving docetaxel based chemotherapy for the treatment of HRPC.

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Immunohistochemical BCL-2 and Ki-67 expression predict survival in prostate cancer patients followed expectantly

Cited by 25 publications

References 18 publications

Human prostate cancer risk factors

Human prostate cancer risk factors

Role and prognostic significance of the Ki‐67 index in non‐Hodgkin's lymphoma

Evidence of a novel docetaxel sensitizer, garlic‐derived S‐allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer

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